Multidimensional Study Designed to Develop a Methodological Framework Based on MRI Data to Predict Pathological Complete Response (pCR) in Patients With Locally Advanced Rectal Cancer After Neoadjuvant Treatment (RESTAGE)

April 10, 2026 updated by: Institut du Cancer de Montpellier - Val d'Aurelle

Rectal cancer presents a significant global health challenge. Despite improvements in clinical outcomes, significant disparities persist across Europe. These differences are explained not only by the heterogeneity of risk factors and screening strategies, but also by variations in diagnostic and therapeutic approaches, which are highly dependent on medical imaging.

Standard treatment for locally advanced rectal cancer based on staging MRI is neoadjuvant treatment (NAT), for tumour downsizing and downstaging, followed by total mesorectal excision. In a significant proportion of cases, radical surgery leads to substantial long-term complications like sexual and urinary dysfunction, fecal incontinence, and impairment in daily activities. Given that up to 42% of patients show complete tumor regression at pathology (i.e. pathological complete response pCR), to avoid unnecessary radical surgery, non-operative management has become an attractive alternative when there are no signs of viable tumour after NAT (i.e. clinical complete response cCR). Such patients are candidates for Watch-and-Wait (W&W), an established active surveillance policy in specialized centers worldwide relying on clinical examination, endoscopy and MRI.

On the other hand, W&W carries a risk of local regrowth (persistence of microscopic residual disease despite apparent cCR). Even in expert hands, assessment of tumor response is not perfect and local regrowth based on current selection methods occurs in ~30% of cases. Although deferred surgery is a successful treatment with no apparent negative impact on local disease control, an increased rate of distant metastases has been recently reported.

Therefore, there is a critical unmet clinical need to detect complete responses after NAT and avoid unnecessary surgery with its associated morbidity and quality of life impairment risks, while also improving sensitivity for residual microscopic disease that will result in local regrowth and associated reduced disease-free survival.

Rectal cancer poses a burden not only on healthcare systems, but also on patient well-being. Patients frequently suffer from feelings of isolation and helplessness when faced with unpredicted disease-related situations, given the common difficulties to access high quality information and communicate with attending physicians. As such, there is a clear need to unburden healthcare facilities from unnecessary hospital visits, while improving patient outcomes, engagement, support and care.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

115

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Preclinical phase: For patients requiring surgery after neoadjuvant chemoradiotherapy, a surgical consultation will be scheduled as part of routine care. The study will be explained, and an information sheet provided. Participation requires signing the informed consent by the patient and the investigating surgeon.

Clinical phase: When a patient requires an MRI as part of their standard care, the study will be presented during the radiology consultation with an information sheet. If the patient agrees to participate, the informed consent form must be signed by the patient and the investigating physician.

Patients may be included in the study at two possible times: during the MRI performed before neoadjuvant treatment (MRI staging), or during the re-evaluation MRI after neoadjuvant treatment (MRI restaging).

Description

Inclusion Criteria for the preclinical phase :

  • Age ≥18 years old;
  • Have a confirmed diagnosis of locally advanced rectal cancer;
  • Have completed neoadjuvant chemoradiotherapy;
  • Be a candidate for surgical treatment with total mesorectal excision;
  • Be willing and able to provide written informed consent;
  • Affiliation to the French Social Security System.

Inclusion criteria for the clinical phase:

  • Age ≥18 years old;
  • Have a confirmed diagnosis of locally advanced rectal cancer;
  • Require neoadjuvant chemoradiotherapy or have completed neoadjuvant chemoradiotherapy;
  • Requires either surgical treatment or a non-surgical strategy ("Watch-and-Wait") after neoadjuvant chemoradiotherapy;
  • Be willing and able to provide written informed consent;
  • Affiliation to the French Social Security System.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Phase 1 (Preclinical): An ex-vivo analysis of surgical specimens
15 surgical specimens will be collected after surgery following neoadjuvant treatment. They will be imaged using a 3T MRI with advanced sequences, then returned to the pathology department. This ex vivo MRI will not affect sample preparation or preservation. MRI images will be aligned with histological sections using non-linear registration to compare MRI parameters with digital pathology data. This step will help identify MRI biomarkers that differentiate healthy tissue, post-treatment fibrotic tissue, and residual tumor. We will assess whether diffusion MRI and relaxometry measurements can predict pathological outcomes by analyzing parameters such as fractional anisotropy, mean diffusivity, and kurtosis, using surgical pathological information when available
Phase 2 (Clinical): An in-vivo clinical MRI study.
The same advanced sequences will be added to MRIs performed during routine clinical care: the initial staging MRI before neoadjuvant chemoradiotherapy, the restaging MRI after treatment completion, and follow-up MRIs for patients managed with a non-operative Watch-and-Wait strategy. For each patient, we will collect imaging data, demographics, medical history, tumor characteristics, treatment details, pathology reports, and clinical follow-up (endoscopy and MRI). All data will be pseudonymized. The second phase involves developing a computational model to predict response to neoadjuvant therapy. A machine learning tool will be designed to predict complete pathological response based on quantitative MRI, standard clinical MRI, and clinical information
Other: questionnaire completion

For all patients, questionnaires will be completed:

  • At the MRI staging if applicable,
  • At the MRI restaging,
  • Every 3 months during the first year; and
  • Every 6 months during the second year.

The following validated questionnaires will be used:

  • EORTC QLQ-C30 (overall quality of life)
  • EORTC QLQ-CR29 (colorectal cancer-specific symptoms)
  • EORTC IN-PATSAT32 (patient satisfaction with care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
developpement and validation of a methodological framework based on advanced MRI data to predict pathological complete response in patients with locally advanced rectal cancer after neoadjuvant treatment
Time Frame: From the baseline to the end of follow up, assessed up to 27 months
using the area under the ROC curve (AUC) to distinguish pathological complete response (pCR) from residual disease.
From the baseline to the end of follow up, assessed up to 27 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
evaluation of the overall diagnostic performance of the predictive model.
Time Frame: From the baseline to the end of follow up, assessed up to 27 months
The overall diagnostic performance of the model will be evaluated using various indicators: Diagnostic accuracy: defined as the overall proportion of correct classifications, Sensitivity, Specificity, Positive predictive value and Negative predictive value
From the baseline to the end of follow up, assessed up to 27 months
identification and validation of new MRI biomarkers capable of distinguishing residual tumor from benign fibrotic tissue, using ex vivo MRI of surgical specimens with direct correlation to histological data.
Time Frame: From the baseline to the end of follow up, assessed up to 27 months
MRI-histology correlation: statistical correlation between advanced MRI data (derived from ex vivo acquisitions) and the corresponding histological measurements of surgical specimens. Regions of interest (ROIs) defined on ex vivo MRI will be matched with digitized histology. This criterion will validate the new biomarkers.
From the baseline to the end of follow up, assessed up to 27 months
establishment of a rectal MRI database to support this project and future research.
Time Frame: From the baseline to the end of follow up, assessed up to 27 months
Establishment of a data registry: creation of a functional, populated database of rectal cancer cases that is compliant with the FAIR principles (Findable, Accessible, Interoperable, Reusable).
From the baseline to the end of follow up, assessed up to 27 months
assessment of the impact of the disease and therapeutic strategies on patients' quality of life.
Time Frame: From the baseline to the end of follow up, assessed up to 27 months
Quality of life scores: scores obtained from standardized questionnaires collected via a digital application to assess the overall impact of the disease and treatments on patients' lives. These will be analyzed using linear mixed models, comparing the surgical group with the "Watch-and-Wait" group over time.
From the baseline to the end of follow up, assessed up to 27 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut du Cancer de Montpellier - Val d'Aurelle

Investigators

  • Study Director: Stephanie NOUGARET, PHD, ICM Co. Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

November 1, 2029

Study Completion (Estimated)

November 1, 2029

Study Registration Dates

First Submitted

February 2, 2026

First Submitted That Met QC Criteria

February 9, 2026

First Posted (Actual)

February 11, 2026

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PROICM 2025-07 RES

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients All participant data collected during the trial, after encoding with an inclusion number, 1st letter of the name and surname may be shared.

The data of the participants will be available upon request and with the completion of a contract between the promoter and the applicant.

The study protocol, the statistical analysis plan (PAS) and the analytical code may also be subject to data sharing as part of a transfer contract (RGPD)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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